1. Field of the Invention
This invention relates to methods of manufacturing medical devices, in particular, stents.
2. Description of the State of the Art
This invention relates to manufacturing of implantable medical devices. These devices include, but are not limited to, radially expandable endoprostheses, that are adapted to be implanted in a bodily lumen. An “endoprosthesis” corresponds to an artificial device that is placed inside the body. A “lumen” refers to a cavity of a tubular organ such as a blood vessel. A stent is an example of such an endoprosthesis. Stents are generally cylindrically shaped devices that function to hold open and sometimes expand a segment of a blood vessel or other anatomical lumen such as urinary tracts and bile ducts. Stents are often used in the treatment of atherosclerotic stenosis in blood vessels. “Stenosis” refers to a narrowing or constriction of a bodily passage or orifice. In such treatments, stents reinforce body vessels and prevent restenosis following angioplasty in the vascular system. “Restenosis” refers to the reoccurrence of stenosis in a blood vessel or heart valve after it has been treated (as by balloon angioplasty, stenting, or valvuloplasty) with apparent success.
Stents are typically composed of scaffold or scaffolding that includes a pattern or network of interconnecting structural elements or struts, formed from wires, tubes, or sheets of material rolled into a cylindrical shape. This scaffolding gets its name because it physically holds open and, if desired, expands the wall of the passageway. Typically, stents are capable of being compressed or crimped onto a catheter so that they can be delivered to and deployed at a treatment site.
Delivery includes inserting the stent through small lumens using a catheter and transporting it to the treatment site. Deployment includes expanding the stent to a larger diameter once it is at the desired location. Mechanical intervention with stents has reduced the rate of restenosis as compared to balloon angioplasty.
Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Medicated stents provide biological therapy through local administration of a therapeutic substance. A medicated stent may be fabricated by coating the surface of either a metallic or polymeric scaffolding with a polymeric carrier that includes an active or bioactive agent or drug. A polymeric scaffolding may also serve as a carrier of an active agent or drug.
These drug eluting stents (DES) are used in order to revascularize occluded regions of the coronary vasculature. Current DES work well yielding single digits of major adverse cardiac events (MACE) and restenosis at one year for a majority of patients. Ongoing issues are restenosis, an iatrogenic disease caused by the intervention itself, and thrombosis. While the onset of restenosis is gradual, stent thrombosis can occur suddenly and the outcome is completely contrary to the intent of revascularization. Stent thrombosis can occur at any time. However, thrombosis which occurs in the first 30 days (subacute) is thought to be due more to procedural issues, blood hypercoaguability, poor stent placement and apposition, and perhaps drug effects. At longer time points, the goal is for the vessel to heal and re-endothelialize to avoid late stent thrombosis occurring beyond 30 days. The ongoing rates of late stent thrombosis have been measured as 0.36 to 0.6% out to five years. Garg S, Serruys P. Coronary Stents. J Amer Coll Cardiol 2010; 56(10): Suppl S. S1.
The only truly non-thrombogenic surface is healthy endothelium. Consequently, rapid and complete re-endotheliazation has always been a goal for metallic, drug eluting, and bioresorbable stents in order to reduce and eliminate late stent thrombosis. As all of the drugs presently used in DES inhibit the proliferation of endothelial cells, the interest in promoting endothelial cell growth remains high. After stenting, re-endotheliatization is achieved primarily by migration of endothelial cells from adjacent arterial areas of intact endothelium. Haudenschild C C, Schutz S M. Lab Invest 1979; 41:407-418; Rogers C, Tseng D Y, et al. Circ Res 1999; 84:378-383. Based on this mechanism, extensive work has been done to understand factors which affect endothelial cell migration. For DES, a major emphasis has been on how to achieve faster, or more complete, endothelial cell migration onto stent struts.